Hydrocortisone Affects Fatigue and Physical Functioning Through Metabolism of Tryptophan: A Randomized Controlled Trial

Freek J H Sorgdrager, Jorien Werumeus Buning, Elske H Bos, André P Van Beek, Ido P Kema
2018 Journal of Clinical Endocrinology and Metabolism  
Precis: Sorgdrager et al. showed that hydrocortisone treatment affected symptoms of fatigue and physical functioning by altering tryptophan metabolism in patients with secondary adrenal insufficiency. Disclosure. The authors report no conflicts of interest in this work. This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. This study is registered with ClinicalTrials.gov, number NCT01546922. Word count: 4191 Abstract:
more » ... : Hydrocortisone (HC) treatment influences health-related quality of life (HRQOL) in secondary adrenal insufficiency (AI). Glucocorticoids regulate tryptophan metabolism through the kynurenine pathway which modulates mood and energy homeostasis. Objective: This study investigated whether tryptophan metabolism mediated the effect of HC dose on HRQOL in patients with secondary AI. Design, Setting and Patients: Forty-seven patients with secondary AI participated in this double-blind randomized controlled cross-over trial in the University Medical Center Groningen. Intervention: Patients were treated for two 10-week periods with a daily HC dose of 0.2 -0.3 mg and 0.4 -0.6 mg/kg body weight, respectively. Main outcome measures: Diary data and questionnaires were used to assess HRQOL. Tryptophan, kynurenine and 3hydroxykynurenine were measured in serum and dialyzed plasma and the kynurenine to tryptophan (kyn/trp) ratio was calculated. Results: A higher dose HC was associated with increased levels of tryptophan (95% CI for mean difference 0.37 to 12.5, p= .038), reduced levels of kynurenine (95% CI -0.49 to -0.10, p= .004) and 3hydroxykynurenine (95% CI -10.6 to -2.35, p= .003) and a reduced kyn/trp ratio (95% CI -0.84 to -0.50, p < .001). The kyn/trp ratio mediated the effect of a higher dose HC on fatigue (p = .041) and physical functioning (p = .005). Conclusion: Metabolism of tryptophan through the kynurenine pathway is reduced after a 10-week treatment with a higher dose HC and plays a role in the effect of HC on fatigue and physical functioning in patients with secondary AI.
doi:10.1210/jc.2018-00582 pmid:29982583 fatcat:walor2yiyffdhdvuotqhcta2e4